Spatial pattern of pulmonary blood flow distribution is stable over days.
Despite the heterogeneous distribution of regional pulmonary perfusion over space, local perfusion remains stable over short time periods (20-100 min). The purpose of this study was to determine whether the spatial distribution of pulmonary perfusion remains stable over longer time periods (1-5 days). Regional blood flow was measured each day for 5 days in five awake standing dogs. Fluorescent microspheres of different colors were injected into a limb vein over 30 s on each day. After the last microsphere injection, the dogs were killed, and lungs were flushed free of blood, excised, dried at total lung capacity, and diced into approximately 2-cm3 pieces (n = 1,296-1,487 per dog). Relative blood flow to each piece on each day was determined by extracting the fluorescent dyes and determining the concentrations of each color. We established that blood flow is spatially heterogeneous with a coefficient of variation of 29.5 +/- 2%. Blood flow to each piece is highly correlated with flow to the same piece on all days (r = 0.930 +/- 0.006). The temporal heterogeneity of regional perfusion as measured by the coefficient of variation is 6.9 +/- 0.7% over the 5 days and is nonrandom. The magnitude of spatial and temporal variation is significantly less than previously reported in a study in which anesthetized and mechanically ventilated dogs were used. We conclude that spatial distribution of pulmonary blood flow remains stable over days and we speculate that in the normal awake dog regional perfusion is determined primarily by a fixed structure such as the geometry of the pulmonary vascular tree rather than by local vasoactive regulators. Anesthesia and/or mechanical ventilation may increase the temporal variability in regional perfusion.


DNA barcodes for Mexican Cactaceae, plants under pressure from wild collecting.
DNA barcodes could be a useful tool for plant conservation. Of particular importance is the ability to identify unknown plant material, such as from customs seizures of illegally collected specimens. Mexican cacti are an example of a threatened group, under pressure because of wild collection for the xeriscaping trade and private collectors. Mexican cacti also provide a taxonomically and geographically coherent group with which to test DNA barcodes. Here, we sample the matK barcode for 528 species of Cactaceae including approximately 75% of Mexican species and test the utility of the matK region for species-level identification. We find that the matK DNA barcode can be used to identify uniquely 77% of species sampled, and 79-87% of species of particular conservation importance. However, this is far below the desired rate of 95% and there are significant issues for PCR amplification because of the variability of primer sites. Additionally, we test the nuclear ITS regions for the cactus subfamily Opuntioideae and for the genus Ariocarpus (subfamily Cactoideae). We observed higher rates of variation for ITS (86% unique for Opuntioideae sampled) but a much lower PCR success, encountering significant intra-individual polymorphism in Ariocarpus precluding the use of this marker in this taxon. We conclude that the matK region should provide useful information as a DNA barcode for Cactaceae if the problems with primers can be addressed, but matK alone is not sufficiently variable to achieve species-level identification. Additional complementary regions should be investigated as ITS is shown to be unsuitable.


Personal best time, not anthropometry or training volume, is associated with total race time in a triple iron triathlon.
The purpose of this study was to investigate in 81 male recreational ultratriathletes (64 finishers and 17 nonfinishers) the relationship of anthropometry, prerace experience, and training with race outcome in a Triple Iron triathlon, using bi and multivariate analyses. In the bivariate analysis, the sum of 8 skinfolds (r = 0.38) and the sum of upper body skinfolds (r = 0.37) were positively related to total race time. None of the anthropometric variables was related to the swim or bike split. Circumference of upper arm (r = 0.42), percent body fat (r = 0.43), the sum of 8 skinfolds (r = 0.47), and the sum of upper body skinfolds (r = 0.45) were positively associated with the time in the run split. None of the training variables was related to total race time or split times. Personal best time in an Ironman triathlon (r = 0.59) and a Triple Iron triathlon (r = 0.82) were positively and highly significantly related to total race time. When all significant variables after bivariate analysis were included in a regression model, personal best time in a Triple Iron triathlon (p < 0.0001) remained the single predictor variable. For practical considerations, athletes with a background as an ultrarunner might have an advantage in successfully finishing a Triple Iron triathlon. However, ultrarunners should also have enough prerace experience in competing in Ironman and Triple Iron triathlons to successfully finish such a race.


Using mass media campaigns to reduce youth tobacco use: a review.
This review synthesizes the published literature on using mass media campaigns to reduce youth tobacco use, with particular focus on effects within population subgroups and the relative effectiveness of campaign characteristics. A search of PubMed and PsycINFO conducted in March of 2014 yielded 397 studies with 34 suitable for inclusion. Included were quantitative studies that evaluate an antitobacco media campaign intended to influence youth cognitions or behavior or explore the relative effectiveness of campaign characteristics among youth. An automated search and assessment of suitability for inclusion was done. Study outcomes were compared and synthesized. Antitobacco media campaigns can be effective across racial/ethnic populations, although the size of the campaign effect may differ by race/ethnicity. Evidence is insufficient to determine whether campaign outcomes differ by socioeconomic status (SES) and population density. Youth are more likely to recall and think about advertising that includes personal testimonials; a surprising narrative; and intense images, sound, and editing. Evidence in support of using a health consequences message theme is mixed; an industry manipulation theme may be effective in combination with a health consequences message. Research is insufficient to determine whether advertising with a secondhand smoke or social norms theme influences youth tobacco use. Our recommendation is to develop antitobacco campaigns designed to reach all at-risk youth, which can be effective across racial/ethnic populations. Research priorities include assessing campaign influence among lower SES and rural youth, disentangling the effects of message characteristics, and assessing the degree to which this body of evidence may have changed as a result of changes in youth culture and communication technology.


Pediatric laryngospasm: prevention and treatment.
The purpose of this review is to discuss the risk factors associated with laryngospasm and the techniques used for prevention and treatment. We also summarize the prevention and treatment modalities in organized algorithms. According to recent endoscopic studies, laryngospasm is always complete, thus airway management and intravenous therapy are indicated. Parental history of children having upper respiratory infection is associated with increased risk of laryngospasm. Anesthesia administered by a pediatric anesthesiologist is associated with lower incidence of laryngospasm. Intravenous anesthesia is associated with lower incidence of laryngospasm than inhalational anesthesia. In tracheal intubation, the use of muscle relaxants decreases laryngospasm. Deep laryngeal mask airway removal is associated with lower incidence of laryngospasm in sevoflurane or isoflurane anesthesia. In no intravenous line situation, laryngospasm can be treated with succinylcholine administration by intramuscular, intraosseous and intralingual routes. Identifying the risk factors and taking the necessary precautions are the key points in prevention of laryngospasm. An experienced anesthesiologist is associated with lower incidence of laryngospasm. Airway management is the most essential part of treatment of laryngospasm. Drugs can be used as an adjunct in treatment of laryngospasm, especially when anesthesia is administered by beginners.


Movement control in patients with shoulder instability: a comparison between patients after open surgery and nonoperated patients.
Open surgery to correct shoulder instability is deemed to facilitate recovery of static and dynamic motor functions. Postoperative assessments focus primarily on static outcomes (e.g., repositioning accuracy). We introduce kinematic measures of arm smoothness to assess shoulder patients after open surgery and compare them with nonoperated patients. Performance among both groups of patients was hypothesized to differ. Postsurgery patients were expected to match healthy controls. All participants performed pointing movements with the affected/dominant arm fully extended at fast, preferred, and slow speeds (36 trials per subject). Kinematic data were collected (100 Hz, 3 seconds), and mixed-design analyses of variance (group, speed) were performed with movement time, movement amplitude, acceleration time, and model-observed similarities as dependent variables. Nonparametric tests were performed for number of velocity peaks. Nonoperated and postsurgery patients showed similarities at preferred and faster movement speeds but not at slower speed. Postsurgery patients were closer to maximally smoothed motion and differed from healthy controls mainly during slow arm movements (closer to maximal smoothness, larger movement amplitude, shorter movement time, and lower number of peaks; i.e., less movement fragmentation). Arm kinematic analyses suggest that open surgery stabilizes the shoulder but does not necessarily restore normal movement quality. Patients with recurrent anterior shoulder instability (RASI) seem to implement a "safe" but nonadaptive mode of action whereby preplanned stereotypical movements may be executed without depending on feedback. Rehabilitation of RASI patients should focus on restoring feedback-based movement control. Clinical assessment of RASI patients should include higher order kinematic descriptors.


IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses.
Although direct-acting antiviral (DAA) treatment results in a sustained virologic response (SVR) in most patients with chronic HCV infection, they are at risk of re-infection. Moreover, the immune system is not completely normalized even after SVR (e.g. increased regulatory T [Treg] cell frequency). We developed a DNA vaccine, GLS-6150, to prevent re-infection of patients with DAA-induced SVR and evaluated its safety and immunogenicity in individuals with chronic HCV infection. GLS-6150 consists of plasmids encoding HCV non-structural proteins (NS3-NS5A) and adjuvant IFNL3. The vaccine was administered 4 times at 4-weekly intervals to 3 groups (1, 3, or 6 mg/vaccination; n = 6 per group), followed by a 6 mg boost at 24 weeks (n = 14). Peripheral blood T cell responses were evaluated by interferon (IFN)-γ enzyme-linked immunospot assays, intracellular cytokine staining, and major histocompatibility complex class-I (MHC-I) dextramer staining. Treg cell frequency was assessed by flow cytometry. Severe adverse events or vaccine discontinuation were not reported. The IFN-γ spot-forming cells specific to NS3-NS5A were increased by GLS-6150. Both CD4+ and CD8+ T cells produced multiple cytokines. However, the frequency and phenotype of HCV-specific MHC-I dextramer+CD8+ T cells were not changed. Interestingly, the frequency of Treg cells, particularly activated Treg cells, was decreased by GLS-6150, as expected from previous reports that IFNL3 adjuvants decrease Treg cell frequency. Ex vivo IFN-λ3 treatment reduced Treg frequency in pre-vaccination peripheral blood mononuclear cells. Finally, Treg cell frequency inversely correlated with HCV-specific, IFN-γ-producing T cell responses in the study participants. We demonstrate that GLS-6150 decreases Treg cell frequency and enhances HCV-specific T cell responses without significant side effects. A phase I clinical trial of GLS-6150 is currently underway in patients with DAA-induced SVR. NCT02027116. Although direct-acting antivirals (DAAs) are successfully used for the treatment of chronic hepatitis C virus (HCV) infection, a prophylactic HCV vaccine needs to be developed, especially for patients who achieve a sustained virologic response. In the current study, we show that a DNA vaccine (GLS-6150) was safe and increased HCV-specific T cell responses. A clinical trial is underway to test this vaccine in patients with a sustained virologic response following DAA therapy.


Restoration of renal function by a novel prostaglandin EP4 receptor-derived peptide in models of acute renal failure.
Acute renal failure (ARF) is a serious medical complication characterized by an abrupt and sustained decline in renal function. Despite significant advances in supportive care, there is currently no effective treatment to restore renal function. PGE(2) is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP(4) receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP(4) receptor, THG213.29, was tested for its efficacy to improve renal function (glomerular filtration rate, renal plasma flow, and urine output) and histological changes in a model of ARF induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats. THG213.29 modulated PGE(2)-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP(4)-mediated relaxation of piglet saphenous vein rings, partially inhibited EP(4)-mediated cAMP production, but did not affect Gα(i) activation or β-arrestin recruitment. In vivo, THG213.29 significantly improved renal function and histological changes in cisplatin- and renal artery occlusion-induced ARF models. THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal cortex; correspondingly, in EP(4)-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP(4)-dependent overexpression of inflammatory IL-6 and of apoptotic death domain-associated protein and BCL2-associated agonist of cell death. Our results demonstrate that THG213.29 represents a novel class of diuretic agent with noncompetitive allosteric modulator effects on EP(4) receptor, resulting in improved renal function and integrity following acute renal failure.


Enhancing research publications using Rich Interactive Narratives.
It is desirable in many disciplines to include supplementary information to add value to research publications, particularly in digital form. The concept of interactive publications, in which the reader can browse and navigate through in a nonlinear manner, is one such medium that is explored in this paper. We describe the application of the Rich Interactive Narrative framework to provide such a mechanism in the fields of archaeology and chemistry, to supplement academic journal papers. This system provides both passive (pre-recorded) and active (user-led) interaction modes to navigate through data, including experimental datasets, maps, photos, video and three-dimensional models, and supports event-based audio and text narration. It includes an extensive authoring tool for deployment to the Web. We conclude by discussing the future possibilities of such a platform for e-science and scholarly communication.


First independent replication of the involvement of LARS2 in Perrault syndrome by whole-exome sequencing of an Italian family.
Perrault syndrome (MIM #233400) is a rare autosomal recessive disorder characterized by ovarian dysgenesis and primary ovarian insufficiency in females, and progressive hearing loss in both genders. Recently, mutations in five genes (HSD17B4, HARS2, CLPP, LARS2 and C10ORF2) were found to be responsible for Perrault syndrome, although they do not account for all cases of this genetically heterogeneous condition. We used whole-exome sequencing to identify pathogenic variants responsible for Perrault syndrome in an Italian pedigree with two affected siblings. Both patients were compound heterozygous for two novel missense variants within the mitochondrial leucyl-tRNA synthetase (LARS2): NM_015340.3:c.899C>T(p.Thr300Met) and c.1912G>A(p.Glu638Lys). Both variants cosegregated with the phenotype in the family. p.Thr300 and p.Glu638 are evolutionarily conserved residues, and are located, respectively, within the editing domain and immediately before the catalytically important KMSKS motif. Homology modeling using as template the E. coli leucyl-tRNA synthetase provided further insights on the possible pathogenic effects of the identified variants. This represents the first independent replication of the involvement of LARS2 mutations in Perrault syndrome, contributing valuable information for the further understanding of this disease.


The economic and clinical efficiency of point-of-care testing for critically ill patients: a decision-analysis model.
Our study objective was to assess economic and clinical outcomes of use of a point-of-care (POC) blood analysis device for postoperative coronary artery bypass graft (CABG) patients. A decision analytic model was developed for patients with high expected use of blood analysis, high potential benefit from rapid turn around time of results, a large annual volume of patients, and substantial expense associated with surgery. Published literature and clinical experts provided incidence, outcome, and cost estimates associated with four clinical scenarios potentially influenced by POC testing (ventricular arrhythmias, cardiac arrest, severe postoperative bleeding, and iatrogenic anemia). We found that changes in clinical outcomes were predominantly dependent on comparative turn around time or CABG patient volume. The positive clinical impact of using POC testing was consistently associated with a positive economic impact. POC blood gas analysis may be associated with decreased incidence of adverse clinical events or earlier detection of such events, resulting in significant cost savings. This study also supports previous findings that the costs of STAT blood analysis are more personnel-related than equipment-related.


Carnitine treatment for stroke in rats.
Changes in the concentrations of carnitine, long-chain acylcoenzyme A, and long-chain acylcarnitine in ischemic myocardium parallel those in ischemic brain. Since carnitine treatment reverses these changes and improves function in ischemic hearts, we examined whether carnitine given to rats before focal cerebral ischemia (produced by tandem right common carotid artery and middle cerebral artery occlusion) alters infarct volume in four separate experiments. Mannitol was used to control for the osmotic effect of carnitine on brain edema in one experiment. While carnitine was found to significantly decrease infarct volume compared with saline in one experiment (p less than 0.05, Student's t test), this result could not be replicated in the subsequent three experiments. Because the positive treatment effect was not reproducible despite similar experimental conditions, the result of the first experiment was attributed to a type I error. Mannitol also showed no significant effect on infarct volume. This study emphasizes the need for concurrent controls with each group of treated animals and the need for replicating the results of a single experiment when testing for drug efficacy in animal models of focal cerebral ischemia.


Tunable coherence-free microwave photonic bandpass filter based on double cross gain modulation technique.
A tunable, coherence-free, high-resolution microwave photonic bandpass filter, which is compatible to be inserted in a conventional fiber optic link, is presented. It is based on using two cross gain modulation based wavelength converters in a recursive loop. The double cross gain modulation technique solves the semiconductor optical amplifier facet reflection problem in the conventional recursive structure; hence the new microwave photonic signal processor has no coherent interference and no phase-induced intensity noise. It allows arbitrary narrow-linewidth telecommunication-type lasers to be used while enabling stable filter operation to be realized. The filter passband frequency can be tuned by using a wavelength tunable laser and a wavelength dependent time delay component. Experimental results demonstrate robust high-resolution bandpass filter operation with narrow-linewidth sources, no phase-induced intensity noise and a high signal-to-noise ratio performance. Tunable coherence-free operation of the high-resolution bandpass filter is also demonstrated.


Long range interactions on wires: a reciprocal space based formalism.
There are many atomic scale systems in materials, chemistry, and biology that can be effectively modeled as finite in two of the physical spatial dimensions and periodically replicated in the third including nanoscale metallic and semiconducting wires, carbon nanotubes, and DNA. However, it is difficult to design techniques to treat long range forces in these systems without truncation or recourse to slowly convergent supercells or computationally inefficient Poisson solvers. In this paper, a rigorous reciprocal space based formalism which permits long range forces on wires to be evaluated simply and easily via a small modification of existing methods for three dimensional periodicity is derived. The formalism is applied to determine long range interactions both between point particles using an Ewald-like approach and the continuous charge distributions that appear in electronic structure calculations. In this way, both empirical force field calculations and, for example, plane-wave based density functional theory computations on wires can be performed easily. The methodology is tested on model and realistic systems including a lithium doped carbon nanotube.


The value of cervical magnetic resonance imaging in the evaluation of the obtunded or comatose patient with cervical trauma, no other abnormal neurological findings, and a normal cervical computed tomography.
The value of magnetic resonance imaging (MRI) in the evaluation of the obtunded or comatose patient with a potential neck injury is a controversial subject. Some authors have suggested that MRI of the cervical spine adds no value in the evaluation of patients with a normal computed tomography (CT) of the neck. However, others have suggested that MRI is the gold standard for clearing the cervical spine in a clinically suspicious or unevaluatable blunt trauma patient. The purpose of this study is to evaluate our data in regard to these conflicting hypotheses. Five consecutive years of data from 17,000 patients seen at our Level I trauma center yielded 512 individuals who underwent both CT and MRI of the cervical spine. Of the latter group, 150 individuals met three strict inclusion criteria for this study: (1) obtundation (Glasgow Coma Scale ≤13, with 94 of this group comatose [Glasgow Coma Scale ≤8]); (2) no obvious neurologic deficits; and (3) a normal cervical CT. The effect of MRI on the clinical management of these patients was evaluated. Among the 150 obtunded or comatose patients with a negative CT, the majority (51%) had a normal MRI. Among the patients with a positive MRI, the most common MRI-positive findings were ligamentous and soft tissue injury (81%). However, no MRI findings were deemed unstable, and no surgical intervention or change in the clinical management aside from collar immobilization of these individuals occurred after MRI. The addition of a cervical MRI to the evaluation protocol of obtunded or comatose patients with an otherwise normal neurologic examination and a normal cervical CT did not provide any additional useful information to change the management of these patients.


Alternative farrowing accommodation: welfare and economic aspects of existing farrowing and lactation systems for pigs.
There is growing societal pressure, expressed through government legislation and consumers' purchasing choices, to abolish livestock systems considered detrimental to farm animal welfare. Such systems include farrowing crates, which are behaviourally and physically restrictive for sows. Therefore, identifying less restrictive farrowing systems for commercial implementation has become an important focus of pig research. Despite numerous attempts to develop indoor alternatives to crates, there is as yet no universal acceptance of such systems at the commercial level. The primary concern is piglet survival, because often favourable figures are reported at the experimental level, but not replicated in commercial evaluation. Alternative farrowing systems should equal or surpass survival levels in conventional systems and perform consistently across a range of farm circumstances for widespread commercial implementation. In addition, it is important that alternatives consider ease of management, operator safety and economic sustainability. Utilising a large database of literature, 12 existing alternative indoor systems were identified and compared against each other, conventional crates and outdoor systems. An assessment of how well alternative systems satisfy the design criteria for meeting animals' biological needs was carried out by developing a welfare design index (WDI). The physical and financial performance of these systems was also evaluated and summarised. The derived WDI yielded values of 0.95 for conventional crates, with higher scores for commercial outdoor systems of 1.10 and indoor group farrowing or multi-suckling systems (e.g. Thorstensson = 2.20). However, the high total piglet mortality (23.7% ± s.e. 2.26) in indoor group systems compared with conventional crates (18.3% ± s.e. 0.63) and outdoor systems (17.0% ± s.e. 2.05), together with the added capital cost (92% more than conventional crates, 249% more than commercial outdoor huts), mainly as a result of extra building space provided per animal, question their feasibility to deliver from an economic perspective. Designed pen systems offered the best compromise, scoring 1.64 from the WDI, with a total piglet mortality of 16.6% (±s.e. 0.88) and capital costs and labour input more comparable to farrowing crates (17.5% more than crates). The critical review of different systems was hampered by the lack of comprehensive data and detailed system descriptions. When attempting to assess welfare and economic attributes of systems, there are certain caveats that require discussion, in particular weighting of the contribution of different design attributes to pig welfare, the relative importance of the sow and her piglets and the many potential confounding factors that arise. Also, when judging any system, it must be emphasised that the maternal characteristics of sows and the quality of stockpersonship will be integral to its success.


Comparative analysis of serotonin receptor (HTR1A/HTR1B families) and transporter (slc6a4a/b) gene expression in the zebrafish brain.
In this study we analyze 5-hydroxytryptamine [5-HT]; serotonin) signaling in zebrafish, an increasingly popular vertebrate disease model. We compare and contrast expression of the 5-HT transporter genes slc6a4a and slc6a4b, which identify 5-HT-producing neurons and three novel 5-HT receptors, htr1aa, htr1ab, and htr1bd. slc6a4a and slc6a4b are expressed in the raphe nuclei, retina, medulla oblongata, paraventricular organ, pretectal diencephalic complex, and caudal zone of the periventricular hypothalamus, in line with the expression profiles of homologues from other vertebrates. Our analysis of serotonin transporter (SERT)-encoding genes also identifies parallel genetic pathways used to build the 5-HT system in zebrafish. In cells in which 5-HT is synthesized by tph1, slc6a4b is used for re-uptake, whereas tph2-positive cells utilize slc6a4a. The receptors htr1aa, htr1ab, and htr1bd also show widespread expression in both the larval and adult brain. Receptor expression is seen in the superior raphe nucleus, retina, ventral telencephalon, optic tectum, thalamus, posterior tuberculum, cerebellum, hypothalamus, and reticular formation, thus implicating 5-HT signaling in several neural circuits. We also examine larval brains double-labeled with 5-HTergic and dopaminergic pathway-specific antibodies, to uncover the identity of some 5-HTergic target neurons. Furthermore, comparison of the expression of transporter and receptor genes also allows us to map sites of autoreceptor activity within the brain. We detect autoreceptor activity in the pretectal diencephalic cluster (htr1aa-, htr1ab-, htr1bd-, and slc6a4a-positive), superior raphe nucleus (htr1aa-, htr1ab-, and slc6a4a-positive), paraventricular organ (htr1aa-, htr1ab-, htr1bd-, and slc6a4b-positive), and the caudal zone of the periventricular hypothalamus (htr1ab- and slc6a4b-positive).


Convergence of cortical and thalamic input to direct and indirect pathway medium spiny neurons in the striatum.
The major afferent innervation of the basal ganglia is derived from the cortex and the thalamus. These excitatory inputs mainly target the striatum where they innervate the principal type of striatal neuron, the medium-sized spiny neurons (MSNs), and are critical in the expression of basal ganglia function. The aim of this work was to test directly whether corticostriatal and thalamostriatal terminals make convergent synaptic contact with individual direct and indirect pathway MSNs. Individual MSNs were recorded in vivo and labelled by the juxtacellular method in the striatum of BAC transgenic mice in which green fluorescent protein reports the expression of dopamine D1 or D2 receptors. After recovery of the neurons, the tissue was immunolabelled for vesicular glutamate transporters type 1 and 2, as markers of cortical and thalamic terminals, respectively. Three of each class of MSNs were reconstructed in 3D and second-order dendrites selected for electron microscopic analysis. Our findings show that direct and indirect pathway MSNs, located in the matrix compartment of the striatum, receive convergent input from cortex and thalamus preferentially on their spines. There were no differences in the pattern of innervation of direct and indirect pathway MSNs, but the cortical input is more prominent in both and synaptic density is greater for direct pathway neurons. The 3D reconstructions revealed no morphological differences between direct and indirect MSNs. Overall, our findings demonstrate that direct and indirect pathway MSNs located in the matrix receive convergent cortical and thalamic input and suggest that both cortical and thalamic inputs are involved in the activation of MSNs.


Automatic interpretation of otoliths using deep learning.
The age structure of a fish population has important implications for recruitment processes and population fluctuations, and is a key input to fisheries-assessment models. The current method of determining age structure relies on manually reading age from otoliths, and the process is labor intensive and dependent on specialist expertise. Recent advances in machine learning have provided methods that have been remarkably successful in a variety of settings, with potential to automate analysis that previously required manual curation. Machine learning models have previously been successfully applied to object recognition and similar image analysis tasks. Here we investigate whether deep learning models can also be used for estimating the age of otoliths from images. We adapt a pre-trained convolutional neural network designed for object recognition, to estimate the age of fish from otolith images. The model is trained and validated on a large collection of images of Greenland halibut otoliths. We show that the model works well, and that its precision is comparable to documented precision obtained by human experts. Automating this analysis may help to improve consistency, lower cost, and increase the extent of age estimation. Given that adequate data are available, this method could also be used to estimate age of other species using images of otoliths or fish scales.


Postmating Female Control: 20 Years of Cryptic Female Choice.
Cryptic female choice (CFC) represents postmating intersexual selection arising from female-driven mechanisms at or after mating that bias sperm use and impact male paternity share. Although biologists began to study CFC relatively late, largely spurred by Eberhard's book published 20 years ago, the field has grown rapidly since then. Here, we review empirical progress to show that numerous female processes offer potential for CFC, from mating through to fertilization, although seldom has CFC been clearly demonstrated. We then evaluate functional implications, and argue that, under some conditions, CFC might have repercussions for female fitness, sexual conflict, and intersexual coevolution, with ramifications for related evolutionary phenomena, such as speciation. We conclude by identifying directions for future research in this rapidly growing field.


[CEOT - Calcified anomalies in dental X-ray. A case-based review of differential diagnoses in radiopaque lesions in maxilla and mandible].
The calcifying epithelial odontogenic tumor (CEOT) is a benign tumor entity, usually localized in the molar region of the lower jaw. CEOT is not known for a destructive growth pattern, nevertheless it grows expansive. To properly diagnose a CEOT, histological verification is necessary. Due to its rare appearance and low incidence (approximately 4 cases per year worldwide), it is usually not diagnosed or thought of at once. Usually it happens to be the "surprising" diagnosis after histological verification. Hereby, we represent a case report of a CEOT - also known as "pindborg" tumor, and discuss the most likely differential diagnoses.


DRIVER REHABILITATION IN PARKINSON'S DISEASE USING A DRIVING SIMULATOR: A PILOT STUDY.
Parkinson's disease (PD) impairs driving performance. In this pilot study, four drivers with PD (selected based on poor road driving performance in the past) participated in a rehabilitation program using a driving simulator. Two different training drives (#1- multiple intersections of varying visibility and traffic load, where an incurring vehicle posed a crash risk, #2- various scenarios on decision making, hazard perception and response) were administered in each session (total 3 sessions once every 1-2 weeks) with immediate feedback after the drives. We observed reduction in crashes in drive #1 and improved scores on drive #2 in the simulator. In addition, 3 subjects showed marked improvements in their total error counts on a standard road test between baseline and post-training sessions, one subject stayed stable. These findings suggest that our simulator training program is feasible and potentially useful in impaired drivers with PD.


Supramolecular chemistry of carbon nano-onions.
Carbon nano-onions (CNOs) are concentric multi-layered fullerenes. Their shape, size and layer count depends on the method of preparation. Their low cytotoxicity allows for high applicability in the biomedical field, in particular, nanomedicine. However, an adequate dispersion of particles in aqueous media is required for the most effective use in this application. Given the hydrophobic nature of pristine CNOs, as is the case with most carbon nanomaterials, they show poor water solubility. Non-covalent functionalisation can be utilised to alter their dispersibility properties, without affecting the intrinsic properties of the sp2 nanomaterial. The use of CNOs in the field of nanomedicine also requires consideration of drug release at the target site. As covalent bonds are inadequate for this purpose, attention is brought towards non-covalent interactions as a viable option for targeted release. This minireview outlines the different methods and approaches for non-covalent modifications of CNOs reported in the literature.


Using real-world data for coverage and payment decisions: the ISPOR Real-World Data Task Force report.
Health decision-makers involved with coverage and payment policies are increasingly developing policies that seek information on "real-world" (RW) outcomes. Motivated by these initiatives, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) created a Task Force on Real-World Data to develop a framework to assist health-care decision-makers in dealing with RW data, especially related to coverage and payment decisions. Task Force cochairs were selected by the ISPOR Board of Directors. Cochairs selected chairs for four working groups on: clinical outcomes, economic outcomes, patient-reported outcomes, and evidence hierarchies. Task Force members included representatives from academia, the pharmaceutical industry, and health insurers. The Task Force met on several occasions, conducted frequent correspondence and exchanges of drafts, and solicited comments on three drafts from a core group of external reviewers and from the ISPOR membership. We defined RW data as data used for decision-making that are not collected in conventional randomized controlled trials (RCTs). We considered several characterizations: by type of outcome (clinical, economic, and patient-reported), by hierarchies of evidence (which rank evidence according to the strength of research design), and by type of data source (supplementary data collection alongside RCTs, large simple trials, patient registries, administrative claims database, surveys, and medical records). Our report discusses eight key issues: 1) the importance of RW data; 2) limitations of RW data; 3) the fact that the level of evidence required depends on the circumstance; 4) the need for good research practices for collecting and reporting RW data; 5) the need for good process in using RW data in coverage and reimbursement decisions; 6) the need to consider costs and benefits of data collection; 7) the ongoing need for modeling; and 8) the need for continued stakeholder dialogue on these topics. Real-world data are essential for sound coverage and reimbursement decisions. The types and applications of such data are varied, and context matters greatly in determining the value of a particular type in any circumstance. It is critical that policymakers recognize the benefits, limitations, and methodological challenges in using RW data, and the need to consider carefully the costs and benefits of different forms of data collection in different situations.


Similarities and differences in gut microbiome composition correlate with dietary patterns of Indian and Chinese adults.
The interaction between diet and gut microbiota, and ultimately their link to health, has turned into the concentration of huge research. However, this relationship still needs to be fully characterized, particularly in case of the Asian population. We compared the fecal bacterial diversity and composition of healthy Indian and Chinese adults, ages 22-35 years, using next-generation sequencing analysis on IlluminaHiSeq 2500 platform. Our analysis revealed unique community structure, dominant Firmicutes, Actinobacteria and underrepresented Bacteroides, of Indian and Chinese gut bacteria. This community structure closely matched with the gut bacterial composition of the Russian population. Therefore, we hypothesized that enrichment of these bacterial clades is supported by high consumption of starch-rich diet such as rice, potato, refined grains. The dominance of genus Bifidobacterium due to carbohydrate-rich diet is another notable feature of this study. Moreover, Indian gut bacteria are significantly represented by Bacteroidetes (p = 0.001) and Prevotella (p = 0.002) in contrast to Chinese, which could be associated with whole grains and plant-based vegetarian diet of Indians. The gut bacterial population of Indian adults were as diverse as Chinese adults (p > 0.1), but significant difference was noticed in gut bacterial composition and relative abundance between two populations (R = 0.625, p < 0.005). Partial least squares discriminant analysis and non-metric multidimensional scaling plots showed dietary habit wise clustering of subjects. Thus, the present work confirms an important role of diet in determining gut bacterial composition. LEfse analysis revealed genera Prevotella, Megasphaera, Catenibacterium, Lactobacillus, Ruminococcus and species Prevotella copri, Lactobacillus ruminis as the potential biomarkers of diet.


Timing of reproduction in a prairie legume: seasonal impacts of insects consuming flowers and seeds.
Seasonal patterns of insect damage to reproductive tissue of the legume Baptisia australis were studied for three years in native tallgrass priairie. Contrasting seasonal patterns of damage were associated with the major species of insect consumers. The moth Grapholitha tristegana (Olethreutidae) and the weevil Tychius sordidus (Curculionidae), which together infested 80-100% of developing fruits (pods), consistently damaged more seeds on average in early than in late maturing pods. But while late opening flowers were less subject to attack from moths and weevils, they were more subject to attack from chewing insects, particularly blister beetles (Epicauta fabricii, Meloidae), which destroyed >80% of all flowers and developing young pods (including moth and weevil larval inhabitants). The blister beetles arrived late in the flowering season and fed particularly on young reproductive tissue, allowing larger, older pods that had developed from early opening flowers to escape destruction. The relative abundances and impacts of blister beetles, moths, and weevils varied from year to year. Adding to the uncertainty of reproductive success of the host plant were the large and variable amounts of damage to immature buds inflicted by insects (including the blister beetles and weevil adults) and late killing frosts. Thus, timing of flowering is critical to success in seed production for B. australis. The heavy impacts of insects and weather can result in a very narrow window in time (which shifts from year to year) during which B. australis can flower with any success. The opposing pressures exerted by insects and weather on floral reproductive success may act in concert with other features of the plant's biology to foster the maintenance of considerable diversity in flowering times among individuals in local populations of B. australis.


The Dilemma of Predicting Violent Radicalization.
Parents, educators, law enforcement officials, and health professionals are all concerned about the violent radicalization of adolescents. Health professionals may be called on to assess teenagers regarding the risk that they will become dangerous. We present a case in which a psychiatrist is asked to do a forensic evaluation of a young adolescent who said troubling things and had some concerning posts on his Facebook page. The evaluation reveals things about both the young boy and his community.


The aliphatic amidase AmiE is involved in regulation of Pseudomonas aeruginosa virulence.
We have previously shown that the eukaryotic C-type natriuretic peptide hormone (CNP) regulates Pseudomonas aeruginosa virulence and biofilm formation after binding on the AmiC sensor, triggering the amiE transcription. Herein, the involvement of the aliphatic amidase AmiE in P. aeruginosa virulence regulation has been investigated. The proteome analysis of an AmiE over-producing strain (AmiE+) revealed an expression change for 138 proteins, including some that are involved in motility, synthesis of quorum sensing compounds and virulence regulation. We observed that the AmiE+ strain produced less biofilm compared to the wild type, and over-produced rhamnolipids. In the same line, AmiE is involved in P. aeruginosa motilities (swarming and twitching) and production of the quorum sensing molecules N-acyl homoserine lactones and Pseudomonas Quinolone Signal (PQS). We observed that AmiE overproduction reduced levels of HCN and pyocyanin causing a decreased virulence in different hosts (i.e. Dictyostelium discoideum and Caenorhabditis elegans). This phenotype was further confirmed in a mouse model of acute lung infection, in which AmiE overproduction resulted in an almost fully virulence decrease. Taken together, our data suggest that, in addition to its role in bacterial secondary metabolism, AmiE is involved in P. aeruginosa virulence regulation by modulating pilus synthesis and cell-to-cell communication.


Aerobic fitness and metabolic health in children: A clinical validation of directly measured maximal oxygen consumption versus performance measures as markers of health.
High aerobic fitness is consistently associated with a favorable metabolic health profile in children. However, measurement of oxygen uptake, regarded as the gold standard for evaluating aerobic fitness, is often not feasible. Thus, the aim of the present study was to perform a clinical validation of three measures of aerobic fitness (peak oxygen consumption [VO2peak] and time to exhaustion [TTE] determined from a graded treadmill protocol to exhaustion, and the Andersen intermittent running test) with clustered metabolic health in 10-year-old children. We included 93 children (55 boys and 38 girls) from Norway during 2012-2013 in the study. Associations between aerobic fitness and three different composite metabolic health scores (including lipoprotein subgroup particle concentrations, triglyceride, glucose, systolic blood pressure, and waist-to-height ratio) were determined by regression analyses adjusting for sex. The relationships among the measures of aerobic fitness were r = 0.78 for VO2peak vs. TTE, r = 0.63 for VO2peak vs. the Andersen test, and r = 0.67 for TTE vs. the Andersen test. The Andersen test showed the strongest associations across all markers of metabolic health (r = - 0.45 to - 0.31, p < 0.002), followed by VO2peak (r = - 0.35 to - 0.12, p < 0.256), and TTE (r = - 0.28 to - 0.10, p < 0.334). Our findings indicate that indirect measures of aerobic fitness do not stand back as markers of metabolic health status in children, compared to VO2peak. This is of great importance as good field tests provide opportunities for measuring aerobic fitness in many settings where measuring VO2peak are impossible.


Endobronchial ultrasound-guided transbronchial needle aspiration for staging of non-small cell lung cancer.
Accurate staging for non-small cell lung cancer (NSCLC) is essential to guide therapy. While computed tomography (CT) and positron emission tomography (PET) scan can indicate whether mediastinal lymphadenopathy is present, histologic confirmation is required to complete the staging evaluation. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique associated with similar diagnostic yield and improved postoperative pain and complication rates compared to mediastinoscopy. We share the surgical technique for EBUS-TBNA based on our experience. An 81-year-old man underwent EBUS-TBNA for concurrent tissue diagnosis and mediastinal staging of a hypermetabolic left lower lobe mass and subcarinal lymph node. Our patient had no perioperative complications and was discharged home on the same day. Histologic evaluation demonstrated squamous cell carcinoma in the left lower lobe and subcarinal lymph node. EBUS-TBNA provides histologic confirmation of suspicious mediastinal lymph nodes seen on imaging. Clinicians should consider EBUS-TBNA as a mediastinal staging modality for patients with NSCLC.


Explaining the harmonic sequence paradox.
According to the harmonic sequence paradox, an expected utility decision maker's willingness to pay for a gamble whose expected payoffs evolve according to the harmonic series is finite if and only if his marginal utility of additional income becomes zero for rather low payoff levels. Since the assumption of zero marginal utility is implausible for finite payoff levels, expected utility theory - as well as its standard generalizations such as cumulative prospect theory - are apparently unable to explain a finite willingness to pay. This paper presents first an experimental study of the harmonic sequence paradox. Additionally, it demonstrates that the theoretical argument of the harmonic sequence paradox only applies to time-patient decision makers, whereas the paradox is easily avoided if time-impatience is introduced.


A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins.
A simple and highly efficient catalytic scavenger of poisonous organophosphorus compounds, based on organophosphorus hydrolase (OPH, EC 18.104.22.168), is produced in aqueous solution by electrostatic coupling of the hexahistidine tagged OPH (His6-OPH) and poly(ethylene glycol)-b-poly(l-glutamic acid) diblock copolymer. The resulting polyion complex, termed nano-OPH, has a spherical morphology and a diameter from 25nm to 100nm. Incorporation of His6-OPH in nano-OPH preserves catalytic activity and increases stability of the enzyme allowing its storage in aqueous solution for over a year. It also decreases the immune and inflammatory responses to His6-OPH in vivo as determined by anti-OPH IgG and cytokines formation in Sprague Dawley rats and Balb/c mice, respectively. The nano-OPH pharmacokinetic parameters are improved compared to the naked enzyme suggesting longer blood circulation after intravenous (iv) administrations in rats. Moreover, nano-OPH is bioavailable after intramuscular (im), intraperitoneal (ip) and even transbuccal (tb) administration, and has shown ability to protect animals from exposure to a pesticide, paraoxon and a warfare agent, VX. In particular, a complete protection against the lethal doses of paraoxon was observed with nano-OPH administered iv and ip as much as 17h, im 5.5h and tb 2h before the intoxication. Further evaluation of nano-OPH as a catalytic bioscavenger countermeasure against organophosphorus chemical warfare agents and pesticides is warranted.


Change during psychotherapy: the perspective of children and adolescents who have been sexually abused.
The aim of this research was to identify the meanings of psychotherapeutic change of children and adolescents who have suffered sexual abuse and were in psychotherapy. In order to do this, a qualitative study was carried out in which in-depth interviews complemented with drawings were conducted with 10 children and adolescents, aged between 6 and 16 years, who were taking part in psychotherapy due to sexual abuse. The interviews took place between 6 and 10 months after the start of the therapy and before it ended. Thematic narrative analysis was used for the interviews and visual narrative analysis for the drawings. The main findings showed that children and adolescents visualized psychotherapeutic change as a process in which gradual progress is made. The participants notice changes from an initial state of sadness and distress, mainly describing a positive shift in terms of emotional well-being. In addition, in this phase of the therapy only a few participants identified changes in their feelings regarding the abusive experience. The participants identified aspects of the therapy and supportive relationships with significant others as elements that foster these changes. In their view, hindering elements include changes of therapist, legal factors, and not being believed by their family. It is discussed the importance of knowing the children and adolescents' perspective regarding psychotherapeutic change while participating in therapy processes, using multiple methodologies, to generate interventions that suit the needs of this population and match the pace of children and adolescents' change.


Online processing of sentences containing noun modification in young children with high-functioning autism.
There is variability in the language of children with autism, even those who are high functioning. However, little is known about how they process language structures in real time, including how they handle potential ambiguity, and whether they follow referential constraints. Previous research with older autism spectrum disorder (ASD) participants has shown that these individuals can use context to access rapidly the meaning of ambiguous words. The severity of autism has also been shown to influence the speed in which children with ASD access lexical information. To understand more about how children with ASD process language in real time (i.e., as it unfolds). The focus was the integration of information and use of referential constraints to identify a referent named in a sentence. We used an eye-tracking task to compare performance between young, high-functioning children with autism (HFA) and children with typical development (TD). A large sample of 5-9-year-old children (mean age = 6;8 years), 48 with HFA and 56 with TD participated; all were attending mainstream schools. For each item participants were shown a display of four images that differed in two dimensions. Each sentence contained an adjective and noun that restricted the choice from four to two (the target and competitor), followed by a prepositional phrase (e.g., the blue square with dots); this added modifying information to provide a unique description of the target. We calculated looking time at the target, the competitor and the two distractors for each 200 ms time interval as children processed the sentence and looked at the display. Generalized estimating equations were used to carry out repeated-measures analyses on the proportion of looking time to target and competitor and time to fixate to target. Children in both groups (HFA and TD) looked at the target and competitor more than at the distractors following the adjective and noun and following the modifying information in the prepositional phrase more at the target. However, the HFA group was significantly slower in both phases and looked proportionally less at the target. Across the sample, IQ and language did not affect the results; however, age and attention had an impact. The older children showed an advantage in processing the information as did the children with higher attention scores. The HFA group took longer than the TD group to integrate the disambiguating information provided in the course of processing a sentence and integrate it with the visual information, indicating that for the ASD group incremental processing was not as advanced as for children with ASD, and they were less sensitive to referential conventions. Training for young children with ASD on the use of referential conventions and available contextual clues may be of benefit to them in understanding the language they hear.


To what extent are carers involved in the care and rehabilitation of patients with hip fracture?
To examine the carer's role regarding early hospital rehabilitation. A qualitative study, using semi-structured interviews with 30 carers. A convenience sample was obtained through participants volunteering for the study. Interviews were of 30 - 45 minutes duration and were audiotaped. The transcripts were read in their entirety by all authors. Main themes were identified and coded. Twenty women and ten men were recruited, who cared for 22 women and eight men. A third of the interviewees reported other caring responsibilities. Carers performed a range of tasks for the patient and most revolved around the key activity of hospital visiting. A range of functions were undertaken, including: help with eating and drinking; providing the opportunity for social interaction; acting as a link between the external world and hospital; and offering emotional support. Carers not only provided practical help but also offered psychological support. Our study highlights the key role of carers in the rehabilitation of patients with hip fracture and provides support for the recommendation that family members should be provided with information regarding rehabilitation. Carers need to be regarded as a resource by hospital staff, given their key role in enhancing patient motivation.


Statewide study of diagnostic agreement in breast pathology.
This study assessed the degree of diagnostic agreement among community-based general pathologists reading slides of representative breast tissue specimens and tested whether diagnostic variability is associated with type of breast specimen (e.g., core needle or excisional biopsy) or slide quality. Twenty-six of the 44 eligible pathologists working at community-based pathology practices in New Hampshire participated. Each pathologist evaluated slides of breast tissue obtained from 30 case subjects randomly selected from a statewide breast pathology database. The diagnostic categories used were benign, benign with atypia, noninvasive malignant, and invasive malignant. The levels of agreement (i.e., kappa coefficients) for the diagnoses were assessed. Agreement was high among pathologists for assignment of diagnostic category (kappa coefficient = 0.71) and was nearly perfect for their selection of benign versus malignant categories (kappa coefficient = 0.95). There was less agreement for the categories of noninvasive malignant and benign with atypia (kappa coefficients of 0.59 and 0.22, respectively). There was no apparent relationship between levels of diagnostic agreement and specimen type or perceived slide quality. Diagnostic agreement for breast tissue specimens is high overall among community-based pathologists, but clinically relevant disagreements may occur in the assessment of noninvasive malignant diagnoses. The establishment of reread policies for certain diagnostic categories may reduce the possibility that diagnostic misclassification will lead to overtreatment or undertreatment. The high degree of diagnostic reproducibility for invasive cancerous lesions of the breast suggests that it is unnecessary for a central review of these lesions in national cancer trials.


A behavioral and pharmacokinetic study of the actions of phenylcyclohexyldiethylamine and its active metabolite, phenylcyclohexylethylamine.
Phenylcyclohexyldiethylamine (PCDE) is an analog of phencyclidine with low affinity for the N-methyl-d-aspartate receptor that is metabolized to an active monoethyl derivative, phenylcyclohexylethylamine (PCE). In a pharmacokinetic analysis of the ataxia response of rats to i.p. administered PCDE and PCE, ataxia intensity was determined together with plasma and cerebrospinal fluid concentrations of the drugs. The role of PCE as the active metabolite of PCDE was assessed quantitatively by correlating the response with both the plasma and cerebrospinal fluid drug levels. Increased PCE concentrations in the cerebrospinal fluid and plasma were associated with increased ataxia response when either PCDE or PCE was the administered drug. However, the concentration-response curves did not superimpose and the curve after PCDE was shifted to the left of that after PCE, suggesting that PCDE was contributing an effect not accountable by PCE concentration. This apparent potentiation must involve an interaction at sites other than the N-methyl-daspartate receptor. In the analysis of the behavior responses, PCDE was found to induce a greater backpedalling response which has been attributed to interaction with dopamine or serotonin systems, suggesting that other transmitter systems may contribute to the overall ataxia response.


Role of carbohydrate-active enzymes in mycorrhizal symbioses.
Mycorrhizal fungi form mutually beneficial interactions with a wide range of terrestrial plants. During this symbiosis, the associated fungus provides mineral nutrients, such as phosphorus and nitrogen, to its host plant in exchange of photosynthesis-derived carbohydrates. Genome sequencing of mycorrhizal fungi has shown that arbuscular mycorrhizal fungi and ectomycorrhizal fungi have a restricted set of plant-cell wall degrading enzymes (PCWDE) genes, while orchid and ericoid mycorrhizal fungi have an extended PCWDE repertoire similar to soil decomposers and wood-decay fungi. On the other hand, mycorrhizal fungi have retained a substantial set of carbohydrate active enzymes (CAZymes) acting on microbial polysaccharides. Functional analysis has shown that several of the remaining PCWDEs are involved in the fungal root colonization and establishment of the symbiotic interface. In this review, we highlight the current knowledge on the evolution and function of PCWDEs in mycorrhizal fungi.


Synthesis, crystal structures, cytotoxicity and qualitative structure-activity relationship (QSAR) of cis-bis{5-[(E)-2-(aryl)-1-diazenyl]quinolinolato}di-n-butyltin(IV) complexes, (n)Bu2Sn(L)2.
A series of cis-bis{5-[(E)-2-(aryl)-1-diazenyl]quinolinolato}di-n-butyltin(IV) complexes has been synthesized and characterized by (1)H-, (13)C-, (119)Sn NMR, ESI-MS (electrospray ionization mass spectrometry), IR and (119m)Sn Mössbauer spectroscopic techniques in combination with elemental analyses. The structures of four di-n-butyltin(IV) complexes, viz., (n)Bu(2)Sn(L(3))(2) (3), (n)Bu(2)Sn(L(4))(2) (4), (n)Bu(2)Sn(L(5))(2) (5) and (n)Bu(2)Sn(L(7))(2).0.5C(6)H(6) (7) (LH=5-[(E)-2-(aryl)-1-diazenyl)quinolin-8-ol) were determined by single crystal X-ray diffraction. In general, the complexes were found to adopt a distorted cis-octahedral arrangement around the tin atom. These complexes retain their solid-state structure in non-coordinating solvent as evidenced by (119)Sn and (13)C NMR spectroscopic results. The in vitro cytotoxicity of di-n-butyltin(IV) complexes (3-8) is reported against seven well characterized human tumour cell lines. The basicity of the two quinolinolato donor N and O atoms of the ligands are discussed in relation to the cytotoxicity data.


Morbidity in neonates of mothers who have ingested aflatoxins.
This study was undertaken to assess whether aflatoxin M(1) concentrations in newborn infants correlated with those of their mothers and to determine whether the presence of aflatoxin M(1) in cord blood was associated with an increase in morbidity in the newborn. There was a strong correlation (r =0.797, p <0.0001) between mothers' and cord blood levels of aflatoxin. There was also a strong negative correlation between aflatoxin levels and birthweight (r =-0.565, p <0.001) but there was no association between aflatoxin M(1) concentration in maternal or cord blood and rates of jaundice or infection.


A cortical area selective for visual processing of the human body.
Despite extensive evidence for regions of human visual cortex that respond selectively to faces, few studies have considered the cortical representation of the appearance of the rest of the human body. We present a series of functional magnetic resonance imaging (fMRI) studies revealing substantial evidence for a distinct cortical region in humans that responds selectively to images of the human body, as compared with a wide range of control stimuli. This region was found in the lateral occipitotemporal cortex in all subjects tested and apparently reflects a specialized neural system for the visual perception of the human body.


urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis.
Glomerulonephritis (GN) is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of renal involvement are imperfect. We investigated 4 urinary proteins as markers of active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL). Patients with active renal AAV (n = 20), active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were identified within a longitudinal cohort. Urinary biomarker concentrations (by ELISA) were normalized for urine creatinine. Marker levels during active AAV were compared to baseline remission levels (from 1-4 visits) for each patient. Areas under receiver-operating characteristic curves (AUC), sensitivities, specificities, and likelihood ratios (LR) comparing disease states were calculated. Baseline biomarker levels varied among patients. All 4 markers increased during renal flares (p < 0.05). MCP-1 discriminated best between active renal disease and remission: a 1.3-fold increase in MCP-1 had 94% sensitivity and 89% specificity for active renal disease (AUC = 0.93, positive LR 8.5, negative LR 0.07). Increased MCP-1 also characterized 50% of apparently nonrenal flares. Change in AGP, KIM-1, or NGAL showed more modest ability to distinguish active renal disease from remission (AUC 0.71-0.75). Hematuria was noted in 83% of active renal episodes, but also 43% of nonrenal flares and 25% of remission samples. Either urinary MCP-1 is not specific for GN in AAV, or it identifies early GN not detected by standard assessment and thus has potential to improve care. A followup study with kidney biopsy as the gold standard is needed.


The protective role of ethnic identity for urban adolescent males facing multiple stressors.
Having a connection to one's ethnic heritage is considered a protective factor in the face of discrimination; however, it is unclear whether the protective effects are persistent across multiple stressors. Furthermore, the dimensions of ethnic identity that reflect group pride/connection (affirmation) and exploration of the meaning of group membership (achievement) may operate differently in the face of stress. The present study examined the moderating role of ethnic identity affirmation and achievement on concurrent and longitudinal relationships between exposure to stress (discrimination, family hardship, exposure to violence) and antisocial behavior in a sample of 256 Black and Latino male youth (70% Black) living in low-income urban neighborhoods. Using regression analysis, concurrent associations were examined at age 18, and longitudinal associations were tested 18 months later. We found that, among youth experiencing discrimination, high levels of achievement and low levels of affirmation predicted greater aggressive behavior and delinquency. Low affirmation also predicted more criminal offending in the face of discrimination. The two dimensions operated similarly in the context of family stress, in which case high levels of affirmation and achievement predicted lower levels of antisocial behavior. The findings suggest a differential role of the two dimensions of ethnic identity with respect to discrimination; furthermore, the coping skills that may be promoted as youth make meaning of their ethnic group membership may serve as cultural assets in the face of family stress.


Double cone dystrophy and RPE degeneration in the retina of the zebrafish gnn mutant.
To characterize morphologic alterations in the retina of the visual mutant zebrafish gantenbein (gnn) and to examine whether these alterations correlate with those present in human hereditary eye diseases. The gnn mutant was isolated by behavioral and macroscopic screening. Retinas of gnn zebrafish larvae were examined at different developmental stages from 2 to 9 days postfertilization (dpf) by standard histologic staining techniques and by immunocytochemistry. Ultrastructural alterations were examined by electron microscopy. The genetic map position of the induced mutation was identified by mapping with two candidate primer pairs on single larvae. The gnn mutant exhibited shortened outer photoreceptor segments and altered RPE morphology. In the photoreceptor layer of the mutant, the total number of lectin-labeled cones was reduced in all developmental stages from 2 to 7 dpf, whereas the amount of rhodopsin-positive cells remained at the wild-type (WT) level. Labeling with zebrafish opsin antibodies revealed dystrophic red cones at 5 dpf, whereas the morphology of all other cone types was largely unaffected. Electron microscopy unveiled electron-dense deposits between the discs of the double cone outer segments. In addition, the onset of progressive RPE degeneration was observed at this stage of development. At later stages, all cone types and the RPE became degenerative. The morphology of distinct second-order neurons remained largely unaffected by the mutation. The gnn mutation was located approximately 4.3 cM from the simple sequence length polymorphism (SSLP) marker Z15453 on linkage group 16. In gnn mutant zebrafish, cones, and especially red cones, are dystrophic in early retinal development. Subsequent to this cone dystrophy, the RPE becomes dysfunctional and starts to degenerate in later stages of development. Thus, the early developmental morphology of gnn exhibits similarities to cone dystrophies most commonly seen in age-related macular degeneration (AMD) among humans, whereas the later stages of degeneration in gnn resemble RPE alterations in retinitis pigmentosa (RP) in humans. The gnn zebrafish mutant may therefore be a useful model for examining the possible interplay and connection between cone dystrophy and RPE degeneration.


Electrical activity and calcium influx regulate ion channel development in embryonic Xenopus skeletal muscle.
The development of electrical excitability involves complex coordinated changes in ion channel activity. Part of this coordination appears to be due to the fact that the expression of some channels is dependent on electrical activity mediated by other channel types. For example, we have previously shown that normal potassium current development in embryonic skeletal muscle cells of the frog Xenopus laevis is dependent on sodium channel activity. To examine the interrelationships between the development of different ionic currents, we have made a detailed study of electrical development in cultured Xenopus myocytes using whole-cell patch-clamp recording. The initial expression of potassium, sodium, and calcium currents is followed by a brief period during which the densities of potassium currents decrease, while at the same time sodium and calcium current densities continue to increase, which may increase electrical excitability during this time. The normal developmental increase in both potassium and sodium currents is inhibited by the sodium channel blocker tetrodotoxin, suggesting that electrical activity normally stimulates the expression of both these currents. These effects of electrical activity appear to be mediated via activation of voltage-gated calcium channels. We suggest that the developmental acquisition of sodium and calcium channels by these cells, possibly coupled with a transient decrease in potassium current density, lead to an increase in electrical excitability and calcium entry, and that this calcium entry provides a critical developmental cue controlling the subsequent development of mature electrical properties.


Atomistic Insight into Tetraalkylphosphonium Bis(oxalato)borate Ionic Liquid/Water Mixtures. 2. Volumetric and Dynamic Properties.
Atomistic molecular dynamics simulations have been performed to investigate volumetric quantities and dynamic properties of binary trihexyltetradecylphosphonium bis(oxalato)borate ([P6,6,6,14][BOB]) ionic liquid (IL)/water mixtures with different water concentrations. The predicted liquid densities for typical [P6,6,6,14][BOB] IL/water mixtures are consistent with available experimental data with a relative discrepancy of less than 3%. The liquid densities and excess molar volumes of all studied [P6,6,6,14][BOB] IL/water mixtures are characterized by concave and convex features, respectively, within full water concentration range. The dynamic properties of [P6,6,6,14] cations, [BOB] anions, and water molecules are particularly analyzed through calculation of velocity autocorrelation functions, diffusion coefficients, and reorientational autocorrelation functions and correlation times. The translational and reorientational mobilities of three species become faster upon increasing water concentration in [P6,6,6,14][BOB] IL/water mixtures and present complex dynamical characteristics arising from three distinct microscopic diffusion features within the full water concentration range. The obtained striking volumetric quantities and particular dynamic properties are well correlated to microscopic liquid structural organization and distinct local ionic environment of all studied [P6,6,6,14][BOB] IL/water mixtures.


Motor Subtypes of Parkinson's Disease Can Be Identified by Frequency Component of Postural Stability.
Parkinson's disease (PD) can be divided into two subtypes based on clinical features-namely tremor dominant (TD) and postural instability and gait difficulty (PIGD). This categorization is important at the early stage of PD, since identifying the subtypes can help to predict the clinical progression of the disease. Accordingly, correctly diagnosing subtypes is critical in initiating appropriate early interventions and tracking the progression of the disease. However, as the disease progresses, it becomes increasingly difficult to further distinguish those attributes that are relevant to the subtypes. In this study, we investigated whether a method using the standing center of pressure (COP) time series data can separate two subtypes of PD by looking at the frequency component of COP (i.e., COP position and speed). Thirty-six participants diagnosed with PD were evaluated, with their bare feet on the force platform, and were instructed to stand upright with their arms by their sides for 20 s (with their eyes open and closed), which is consistent with the traditional COP measures. Fast Fourier transform (FFT) and wavelet transform (WT) were performed to distinguish between the motor subtypes using the COP measures. The TD group exhibited larger amplitudes at the frequency range of 3-7 Hz when compared to the PIGD group. Both the FFT and WT methods were able to differentiate the subtypes. COP time series information can be used to differentiate between the two motor subtypes of PD, using the frequency component of postural stability.


Carbon stable isotopic composition of soluble sugars in Tillandsia epiphytes varies in response to shifts in habitat.
We studied C stable isotopic composition (delta(13)C) of bulk leaf tissue and extracted sugars of four epiphytic Tillandsia species to investigate flexibility in the use of crassulacean acid metabolism (CAM) and C(3) photosynthetic pathways. Plants growing in two seasonally dry tropical forest reserves in Mexico that differ in annual precipitation were measured during wet and dry seasons, and among secondary, mature, and wetland forest types within each site. Dry season sugars were more enriched in (13)C than wet season sugars, but there was no seasonal difference in bulk tissues. Bulk tissue delta(13)C differed by species and by forest type, with values from open-canopied wetlands more enriched in (13)C than mature or secondary forest types. The shifts within forest habitat were related to temporal and spatial changes in vapor pressure deficits (VPD). Modeling results estimate a possible 4% increase in the proportional contribution of the C(3) pathway during the wet season, emphasizing that any seasonal or habitat-mediated variation in photosynthetic pathway appears to be quite moderate and within the range of isotopic effects caused by variation in stomatal conductance during assimilation through the C(3) pathway and environmental variation in VPD. C isotopic analysis of sugars together with bulk leaf tissue offers a useful approach for incorporating short- and long-term measurements of C isotope discrimination during photosynthesis.


Moving knowledge into action for more effective practice, programmes and policy: protocol for a research programme on integrated knowledge translation.
Health research is conducted with the expectation that it advances knowledge and eventually translates into improved health systems and population health. However, research findings are often caught in the know-do gap: they are not acted upon in a timely way or not applied at all. Integrated knowledge translation (IKT) is advanced as a way to increase the relevance, applicability and impact of research. With IKT, knowledge users work with researchers throughout the research process, starting with identification of the research question. Knowledge users represent those who would be able to use research results to inform their decisions (e.g. clinicians, managers, policy makers, patients/families and others). Stakeholders are increasingly interested in the idea that IKT generates greater and faster societal impact. Stakeholders are all those who are interested in the use of research results but may not necessarily use them for their own decision-making (e.g. governments, funders, researchers, health system managers and policy makers, patients and clinicians). Although IKT is broadly accepted, the actual research supporting it is limited and there is uncertainty about how best to conduct and support IKT. This paper presents a protocol for a programme of research testing the assumption that engaging the users of research in phases of its production leads to (a) greater appreciation of and capacity to use research; (b) the production of more relevant, useful and applicable research that results in greater impact; and (c) conditions under which it is more likely that research results will influence policy, managerial and clinical decision-making. The research programme will adopt an interdisciplinary, international, cross-sector approach, using multiple and mixed methods to reflect the complex and social nature of research partnerships. We will use ongoing and future natural IKT experiments as multiple cases to study IKT in depth, and we will take advantage of the team's existing relationships with provincial, national and international organizations. Case studies will be retrospective and prospective, and the 7-year grant period will enable longitudinal studies. The initiation of partnerships, funding processes, the research lifecycle and then outcomes/impacts post project will be studied in real time. These living laboratories will also allow testing of strategies to improve the efficiency and effectiveness of the IKT approach. This is the first interdisciplinary, systematic and programmatic research study on IKT. The research will provide scientific evidence on how to reliably and validly measure collaborative research partnerships and their impacts. The proposed research will build the science base for IKT, assess its relationship with research use and identify best practices and appropriate conditions for conducting IKT to achieve the greatest impact. It will also train and mentor the next generation of IKT researchers.


Changes in sensitivity patterns to selected antibiotics in Clostridium difficile in geriatric in-patients over an 18-month period.
Clostridium difficile-associated disease continues to be a major problem in hospitals and long-term care facilities throughout the developed world. Administration of certain antibiotics such as amoxycillin, oral cephalosporins and clindamycin is associated with the greatest risk of developing C. difficile disease. The two antibiotics used for treatment of C. difficile disease are vancomycin and metronidazole, to which there is currently very little resistance. Randomly selected isolates (186) from 90 patients being investigated during an 18-month epidemiological study into the disease were tested for their susceptibility to vancomycin, metronidazole, amoxycillin, clindamycin, cefoxitin and ceftriaxone by the NCCLS agar dilution method. There was a narrow range of MIC for the two treatment agents (vancomycin and metronidazole), from 0.5 to 4 microg ml(-1), with no evidence of resistance. All strains were resistant to cefoxitin (MIC 64-256 microg ml(-1)), the antibiotic used in most selective media. All strains were of similar sensitivity to amoxycillin (MIC(90)= 4 microg ml(-1)). Most strains were resistant to ceftriaxone (MIC > or = 64 microg ml(-1)) or of intermediate resistance (MIC > or = 32 microg ml(-1)), with only two sensitive strains (MIC 16 microg ml(-1)). Clindamycin resistance was common, with 67 % of strains resistant (MIC > or = 8 microg ml(-1)), 25 % with intermediate resistance (MIC > or = 4 microg ml(-1)) and only 8 % sensitive (MIC < or = 2 microg ml(-1)). Twelve isolates from six different patients had very high resistance to clindamycin (MIC > or = 128 microg ml(-1)). Multiple isolates from the same patient, taken at different times, showed changes in susceptibility patterns over time. The only major change in susceptibility over the time-period was in clindamycin resistance; some strains appeared to become more resistant while others became less resistant. No differences were seen in the MIC(50) and MIC(90) of the different S-types of C. difficile identified, although some S-types were present in very small numbers. There was no correlation between the antibiotics prescribed and susceptibility.


Socio-demographic predictors and average annual rates of caesarean section in Bangladesh between 2004 and 2014.
Globally the rates of caesarean section (CS) have steadily increased in recent decades. This rise is not fully accounted for by increases in clinical factors which indicate the need for CS. We investigated the socio-demographic predictors of CS and the average annual rates of CS in Bangladesh between 2004 and 2014. Data were derived from four waves of nationally representative Bangladesh Demographic and Health Survey (BDHS) conducted between 2004 and 2014. Rate of change analysis was used to calculate the average annual rate of increase in CS from 2004 to 2014, by socio-demographic categories. Multi-level logistic regression was used to identify the socio-demographic predictors of CS in a cross-sectional analysis of the 2014 BDHS data. CS rates increased from 3.5% in 2004 to 23% in 2014. The average annual rate of increase in CS was higher among women of advanced maternal age (≥35 years), urban areas, and relatively high socio-economic status; with higher education, and who regularly accessed antenatal services. The multi-level logistic regression model indicated that lower (≤19) and advanced maternal age (≥35), urban location, relatively high socio-economic status, higher education, birth of few children (≤2), antenatal healthcare visits, overweight or obese were the key factors associated with increased utilization of CS. Underweight was a protective factor for CS. The use of CS has increased considerably in Bangladesh over the survey years. This rising trend and the risk of having CS vary significantly across regions and socio-economic status. Very high use of CS among women of relatively high socio-economic status and substantial urban-rural difference call for public awareness and practice guideline enforcement aimed at optimizing the use of CS.


The in vitro and in vivo cardiovascular effects of Delta9-tetrahydrocannabinol in rats made hypertensive by chronic inhibition of nitric-oxide synthase.
Evidence suggests that Delta9-tetrahydrocannabinol (THC) may have antihypertensive effects and that the vasodilator effect of endocannabinoids is enhanced in rats made hypertensive by chronic NO synthase inhibition. Therefore, the aims of the present study were to investigate whether the in vitro and in vivo cardiovascular responses to THC are altered by Nomega-nitro-L-arginine methyl ester (L-NAME) treatment. The vasorelaxant effects of THC were enhanced in small mesenteric arteries from L-NAME-treated rats. This enhanced response was not inhibited by cannabinoid CB1 receptor antagonism [1 microM N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; AM251]. Pretreating vessels with the transient receptor potential vanilloid receptor receptor agonist capsaicin at 10 microM for 1 h reduced vasorelaxation to THC to a greater extent in L-NAME-treated than control rats. Inhibition of cyclooxygenase with 10 microM indomethacin inhibited THC responses in arteries from L-NAME-treated rats but not from control rats. In conscious, chronically instrumented rats, 1 mg kg-1 i.v. THC caused a pressor effect, with vasoconstriction of the renal and mesenteric vascular beds, and hindquarters vasodilatation. Pretreatment with 3 mg kg-1 i.v. AM251 reduced the pressor and vasoconstrictor effects of THC, abolished the hindquarters vasodilatation, and revealed a bradycardic response. L-NAME-treated rats showed similar pressor and vasoconstrictor responses to THC, but with bradycardia, and reduced hindquarter vasodilatation. These data show that, in vitro, isolated arteries of L-NAME-treated rats show enhanced vasorelaxant responses to THC through an increased sensory nerve component and stimulation of prostanoids. However, in vivo, THC causes a CB1 receptor-mediated pressor effect with hindquarters vasodilatation. There was no evidence of enhanced vasodilator effects of THC in L-NAME-treated animals in vivo.


Down syndrome: national conference on patient registries, research databases, and biobanks.
A December 2010 meeting, "Down Syndrome: National Conference on Patient Registries, Research Databases, and Biobanks," was jointly sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH) in Bethesda, MD, and the Global Down Syndrome Foundation (GDSF)/Linda Crnic Institute for Down Syndrome based in Denver, CO. Approximately 70 attendees and organizers from various advocacy groups, federal agencies (Centers for Disease Control and Prevention, and various NIH Institutes, Centers, and Offices), members of industry, clinicians, and researchers from various academic institutions were greeted by Drs. Yvonne Maddox, Deputy Director of NICHD, and Edward McCabe, Executive Director of the Linda Crnic Institute for Down Syndrome. They charged the participants to focus on the separate issues of contact registries, research databases, and biobanks through both podium presentations and breakout session discussions. Among the breakout groups for each of the major sessions, participants were asked to generate responses to questions posed by the organizers concerning these three research resources as they related to Down syndrome and then to report back to the group at large with a summary of their discussions. This report represents a synthesis of the discussions and suggested approaches formulated by the group as a whole.


First description of deep benthic habitats and communities of oceanic islands and seamounts of the Nazca Desventuradas Marine Park, Chile.
Seamounts and oceanic islands of the Chilean Exclusive Economic Zone at the intersection of the Nazca and Salas y Gómez ridges lie within one of the least explored areas in the world. The sparse information available, mainly for seamounts outside Chilean jurisdiction and shallow-water fauna of the Desventuradas Islands, suggests that the area is a hotspot of endemism. This apparent uniqueness of the fauna motivated the creation of the large Nazca-Desventuradas Marine Park (NDMP, ~ 300,000 km2) around the small islands San Felix and San Ambrosio in 2015. We report for the first time a detailed description of benthic microhabitats (i.e., centimeter to meter scale), macrohabitats (i.e., meter to kilometer-scale) and associated megafauna within the NDMP. Descriptions were based on analysis of fauna collected by trawling and ROV video observations from ~ 50 to 370 m depth. Rocky, coarse sand and silty sediment bottom habitats were observed at island slopes. In contrast, rocky and coarse sandy bottom habitats with a predominance of rhodoliths, thanatocoenosis, and other biogenic components were observed at seamounts. Mobile fauna and predators dominated the oceanic islands and nearby seamounts, whereas seamounts farther from the islands were dominated by sessile and hemisessile fauna that were mainly suspension and deposit feeders. Based on the register of 118 taxonomic units, our results provide an expanded and updated baseline for the benthic biodiversity of NDMP habitats, which seemed pristine, without evidence of trawling or anthropogenic debris.


Studies on the effect of angiotensin II and of Des -angiotensin II on blood pressure, plasma renin activity and plasma aldosterone in the dog.
1. The effect of infusions of equimolar doses of angiotensin II (AII) and of Des -angiotensin II (heptapeptide) on plasma renin activity, blood pressure and plasma aldosterone were compared in normal anaesthetized dexamethasone-suppressed dogs. 2. Plasma renin activity was equally suppressed by both compounds. The increase in blood pressure induced by the heptapeptide averaged 43-62% of the increase during AII infusions. No significant differences in aldosterone increase were observed between AII and the heptapeptide. Plasma aldosterone, however, dropped significantly faster in heptapeptide-treated dogs after the end of the infusions. 3. Sar -Ala -angiotensin II (saralasin, 400 pmol min-1 kg-1) suppressed plasma aldosterone that was stimulated by heptapeptide (20 pmol min-1 kg-1) completely. The same angiotensin antagonist had only a moderate effect on plasma aldosterone stimulated by AII. After stopping the antagonist infusion, plasma aldosterone rose significantly higher in dogs infused with AII than in those receiving the heptapeptide. 4. The results demonstrate differences between the effects of AII and the heptapeptide both on blood pressure and on plasma aldosterone. They do not support the hypothesis that the heptapeptide may be the main mediator of aldosterone secretion.


Playing the Long Game: Considering the Future of Augmentative and Alternative Communication Research and Service.
This article examines the growth of aided augmentative and alternative communication (AAC) in providing support to children and youth with significant communication needs. Addressing current trends and offering a discussion of needs and probable future advances is framed around five guiding principles initially introduced by Williams, Krezman, and McNaughton. These include: (1) communication is a basic right and the use of AAC, especially at a young age, can help individuals realize their communicative potential; (2) AAC, like traditional communication, requires it to be fluid with the ability to adapt to different environments and needs; (3) AAC must be individualized and appropriate for each user; (4) AAC must support full participation in society across all ages and interests; and (5) individuals who use AAC have the right to be involved in all aspects of research, development, and intervention. In each of these areas current advances, needs, and future predictions are offered and discussed in terms of researchers' and practitioners' efforts to a continued upward trajectory of research and translational service delivery.


Nucleophilic versus Electrophilic Activation of Hydrogen Peroxide over Zr-Based Metal-Organic Frameworks.
Zr-based metal-organic frameworks (Zr-MOF) UiO-66 and UiO-67 catalyze thioether oxidation in nonprotic solvents with unprecedentedly high selectivity toward corresponding sulfones (96-99% at ca. 50% sulfide conversion with only 1 equiv of H2O2). The reaction mechanism has been investigated using test substrates, kinetic, adsorption, isotopic (18O) labeling, and spectroscopic tools. The following facts point out a nucleophilic character of the peroxo species responsible for the superior formation of sulfones: (1) nucleophilic parameter XNu = 0.92 in the oxidation of thianthrene 5-oxide and its decrease upon addition of acid; (2) sulfone to sulfoxide ratio of 24 in the competitive oxidation of methyl phenyl sulfoxide and p-Br-methyl phenyl sulfide; (3) significantly lower initial rates of methyl phenyl sulfide oxidation relative to methyl phenyl sulfoxide (kS/kSO = 0.05); and (4) positive slope ρ = +0.42 of the Hammett plot for competitive oxidation of p-substituted aryl methyl sulfoxides. Nucleophilic activation of H2O2 on Zr-MOF is also manifested by their capability of catalyzing epoxidation of electron-deficient C═C bonds in α,β-unsaturated ketones accompanied by oxidation of acetonitrile solvent. Kinetic modeling on methyl phenyl sulfoxide oxidation coupled with adsorption studies supports a mechanism that involves the interaction of H2O2 with Zr sites with the formation of a nucleophilic oxidizing species and release of water followed by oxygen atom transfer from the nucleophilic oxidant to sulfoxide that competes with water for Zr sites. The nucleophilic peroxo species coexists with an electrophilic one, ZrOOH, capable of oxygen atom transfer to nucleophilic sulfides. The predominance of nucleophilic activation of H2O2 over electrophilic one is, most likely, ensured by the presence of weak basic sites in Zr-MOFs identified by FTIR spectroscopy of adsorbed CDCl3 and quantified by adsorption of isobutyric acid.


Commentary on the clinical management of metabolic syndrome: why a healthy lifestyle is important.
Metabolic syndrome (MS) is associated with an increased risk of type 2 diabetes mellitus and cardiovascular diseases. There is no recognized method to manage MS. Many physicians treat the individual characteristics of MS (high blood pressure, high triglycerides, and so on) instead of the syndrome as a whole, placing particular emphasis on those components that are easily amenable to drug treatment. However, regular physical exercise and a healthy diet have been demonstrated to improve the health of a number of populations, but few studies have assessed their effects in patients with MS. A meta-analysis by Yamaoka and Tango in BMC Medicine found that a lifestyle change program (dietary counseling and encouragement to exercise) resulted in improvements in components of MS and in reducing the proportion of patients with MS. The effects may not be impressive in absolute terms, but the data should be interpreted with the heterogeneity of the included studies in mind. Because of the many adverse side effects of the drugs used to correct individual aspects of MS, this meta-analysis provides strong evidence that lifestyle changes must be the first-line approach to manage MS.See related article http://www.biomedcentral.com/1741-7015/10/138/abstract.


Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III.
Several biomarkers have been proposed as useful parameters to better specify the prognosis or to delineate new target therapy strategies for glioblastoma patients. MicroRNAs could represent putative target molecules, considering their role in tumorigenesis, cancer progression and their specific tissue expression. Although several studies have tried to identify microRNA signature for glioblastoma, a microRNA profile is still far from being well-defined. In this work the expression of 19 microRNAs (miR-7, miR-9, miR-9∗, miR-10a, miR-10b, miR-17, miR-20a, miR-21, miR-26a, miR-27a, miR-31, miR-34a, miR-101, miR-137, miR-182, miR-221, miR-222, miR-330, miR-519d) was evaluated in sixty formalin-fixed and paraffin-embedded glioblastoma samples using a locked nucleic acid real-time PCR. Moreover, a comparison of miRNA expressions was performed between primary brain neoplasias of different grades (grades IV-I). The analysis of 14 validated miRNA expression in the 60 glioblastomas, using three different non-neoplastic references as controls, revealed a putative miRNA signature: mir-10b and miR-21 were up-regulated, while miR-7, miR-31, miR-101, miR-137, miR-222 and miR-330 were down-regulated in glioblastomas. Comparing miRNA expression between glioblastoma group and gliomas of grades I-III, 3 miRNAs (miR-10b, mir-34a and miR-101) showed different regulation statuses between high-grade and low-grade tumors. miR-10b was up-regulated in high grade and significantly down-regulated in low-grade gliomas, suggesting that could be a candidate for a GBM target therapy. This study provides further data for the identification of a miRNA profile for glioblastoma and suggests that different-grade neoplasia could be characterized by different expression of specific miRNAs.


Improving management of obesity in primary care: cluster randomised trial.
To evaluate a training programme intended to improve the management of obesity, delivered to general practice teams. Cluster randomised trial. Northern and Yorkshire region of England. 44 general practices invited consecutively attending obese adults to participate; 843 patients attended for collection of baseline data and were subsequently randomised. 4.5 hour training programme promoting an obesity management model. Difference in weight between patients in intervention and control groups at 12 months (main outcome measure) and at 3 months and 18 months; change in practitioners' knowledge and behaviour in obesity management consultations. Twelve months after training the patients in the intervention group were 1 (95% confidence interval--1.9 to 3.9) kg heavier than controls (P = 0.5). Some evidence indicated that practitioners' knowledge had improved. Some aspects of the management model, including recording weight, target weight, and dietary targets, occurred more frequently in intervention practices after the training, but in absolute terms levels of implementation were low. A training package promoting a brief, prescriptive approach to the treatment of obesity through lifestyle modification, intended to be incorporated into routine clinical practice, did not ultimately affect the weight of this motivated and at risk cohort of patients.


Older Adults' Medication Management in the Home: How can Robots Help?
Successful management of medications is critical to maintaining healthy and independent living for older adults. However, medication non-adherence is a common problem with a high risk for severe consequences [5], which can jeopardize older adults' chances to age in place [1]. Well-designed robots assisting with medication management tasks could support older adults' independence. Design of successful robots will be enhanced through understanding concerns, attitudes, and preferences for medication assistance tasks. We assessed older adults' reactions to medication hand-off from a mobile manipulator robot with 12 participants (68-79 yrs). We identified factors that affected their attitudes toward a mobile manipulator for supporting general medication management tasks in the home. The older adults were open to robot assistance; however, their preferences varied depending on the nature of the medication management task. For instance, they preferred a robot (over a human) to remind them to take medications, but preferred human assistance for deciding what medication to take and for administering the medication. Factors such as perceptions of one's own capability and robot reliability influenced their attitudes.